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Originally published online as doi:10.1189/jlb.0209094 on July 13, 2009

Published online before print July 13, 2009
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(Journal of Leukocyte Biology. 2009;86:779-793.)
© 2009 Society for Leukocyte Biology

Obstacles to the successful development of an efficacious T cell-inducing HIV-1 vaccine

Larissa Herkenhoff Haut*,{dagger} and Hildegund C. J. Ertl{dagger},1

* Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil; and
{dagger} Wistar Institute, Philadelphia, Pennsylvania, USA

1. Correspondence: The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USA. E-mail: ertl{at}wistar.upenn.edu

An efficacious vaccine to HIV-1 is direly needed to stem the global pandemic. Immunogens that elicit broadly cross-neutralizing antibodies to HIV-1 remain elusive, and thus, most HIV-1 vaccine efforts are focusing on induction of T cells. The notion that T cells can mediate protection against HIV-1 has been called into question by the failure of the STEP trial, which was designed to test this concept by the use of an E1-deleted Ad vaccine carrier. Lack of efficacy of the STEP trial vaccine underscores our limited knowledge about correlates of immune protection against HIV-1 and stresses the need for an enhanced commitment to basic research, including preclinical and clinical vaccine studies. In this review, we discuss known correlates of protection against HIV-1 and different vaccine strategies that have been or are being explored to induce such correlates, focusing on T cell-inducing vaccines and particularly on Ad vectors.

Key Words: correlates of protection • adenovirus vectors • STEP trial • animal models